Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg-1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

Health related quality of life in patients with community-acquired pneumococcal pneumonia in France.

BACKGROUND: Community Acquired Pneumococcal Pneumonia is a lung infection that causes serious health problems and can lead to complications and death. The aim of this study was to observe and analyze health related quality of life after a hospital episode for patients with community acquired pneumococcal pneumonia in France. METHODS: A total of 524 individuals were enrolled prospectively in the study and were followed for 12 months after hospital discharge. Presence of streptococcus pneumoniae was confirmed by microbiological sampling. Quality of life was reported at four different points of time with the EQ-5D-3 L health states using the French reference tariff. Complete data on all four periods was available for 269 patients. We used descriptive and econometric analysis to assess quality of life over time during follow-up, and to identify factors that impact the utility indexes and their evolution through time. We used Tobit panel data estimators to deal with the bounded nature of utility values. RESULTS: Average age of patients was 63 and 55% of patients were men. Negative predictors of quality of life were the severity of the initial event, history of pneumonia, smokers, age and being male. On average, quality of life improved in the first 6 months after discharge and stabilized beyond. At month 1, mean utility index was 0.53 (SD: 0.34) for men and 0.45 (SD: 0.34) for women, versus mean of 0.69 (SD: 0.33) and 0.70 (SD: 0.35) at Month 12. "Usual activities" was the dimension the most impacted by the disease episode. Utilities for men were significantly higher than for women, although male patients were more severe. Individuals over 85 years old did not improve quality of life during follow-up, and quality of life did not improve or deteriorated for 34% of patients. We found that length of hospital stay was negatively correlated with quality of life immediately after discharge. CONCLUSION: This study provides with evidence that quality of life after an episode of community acquired pneumococcal pneumonia improves overall until the sixth month after hospital discharge, but older patients with previous history of pneumonia may not experience health gains after the initial episode.

Angiomatoid fibrous histiocytoma of the pulmonary artery: a multidisciplinary discussion.

AIMS: Angiomatoid fibrous histiocytoma (AFH) is a rare neoplastic disease usually occurring in the dermis or subcutis of the extremities of young adults or children. Although sporadic cases in deep soft tissue and visceral organs have been reported, we present here the first description of AFH developing in a large artery. METHODS AND RESULTS: Paraffin sections of the surgical specimen were stained with haematoxylin and eosin, and immunohistochemistry was performed (CKAE1/AE3, EMA, CD34, p63, CD38, smooth muscle actin, and desmin). In addition, FISH and RT-PCR were applied in order to check for EWRS rearrangement. The histomorphological features, and FISH analysis revealing rearrangement of EWSR, indicated the definitive diagnosis of AFH. RT-PCR confirmed EWSR rearrangement, and detected an EWSR1-ATF1 fusion transcript. CONCLUSIONS: A thoracic location of AFH has not been reported until very recently, and shares a differential diagnosis with diverse neoplasms, including spindle cell carcinoma and low-grade sarcoma. We describe the first reported case of thoracic AFH arising in a large vessel, and highlight distinctive histological and molecular features.

Costs associated with community acquired pneumonia in France.

OBJECTIVES: Pneumocost is a prospective study that aimed at documenting the costs of the management of patients hospitalized with a pneumococcal pneumonia and the post-discharge costs during a 6-month period in the French context. METHODS: Billing data were used to document hospital costs. Resource use during the follow-up period was collected through phone interviews at month 1, 3 and 6. Descriptive statistics and multivariate analyses were performed. We used generalized linear models with log-link functions to estimate parameters associated with hospital and follow-up costs of patients. RESULTS: Five hundred twenty-four patients were enrolled in 40 public centers from October 2011 to April 2014. Average age was 63 (SD 17); 55.0% of them were male. Average length of stay was 15 days (SD 23). Average cost of stay for the French Sickness Fund was €7293 (SD €7363). Average cost of follow-up was €1242 (SD €3000) and decreased steadily through time. When controlling for patient's socioeconomic characteristics, severity of disease and hospital stay, results showed a concave relationship between hospital costs and age. Obesity, the severity of the disease and comorbidities were associated with constantly increasing inpatient costs. Concerning follow-up costs, we found the same concave relationship with age, while gender, a history of pneumonia and severity of the disease were the most important predictors of high costs after discharge. CONCLUSION: Pneumocost is the first French study providing a robust estimation of the cost of managing invasive pneumococcal pneumonia in the French context.

Levofloxacin 500 mg once daily versus cefuroxime 250 mg twice daily in patients with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and exacerbation-free interval.

The long-term outcome time to relapse determined as the exacerbation-free interval (EFI) has been proposed as a standard measure for comparing the efficacy of antimicrobial therapies in acute exacerbation of chronic obstructive bronchitis (AECOB). In this 6-month, randomised, open-label study, the efficacy of 10 days of oral levofloxacin 500 mg once daily or cefuroxime 250 mg twice daily was evaluated in 689 well-defined patients experiencing AECOB episodes. In the clinically evaluable per-protocol (PPc) population and the modified intent-to-treat population, the clinical cure rates at test of cure were, respectively, 94.6% for levofloxacin versus 93.8% for cefuroxime (0.8% difference, 95% confidence interval (CI) -3.2 to 4.8) and 94.5% for levofloxacin versus 92.2% for cefuroxime (2.3% difference, 95% CI -1.8 to 6.2), whilst the probability that 25% of patients would relapse during follow-up was reached within 93 days for levofloxacin compared with 81 days for cefuroxime in the PPc population (P=0.756). A multivariate analysis revealed that only congestive heart failure and number of AECOB episodes in the previous 12 months were predictive of relapse. Safety was comparable in the two treatment groups, with possibly related treatment-emergent adverse events occurring in 5.0% and 2.9% of subjects in the levofloxacin and cefuroxime groups, respectively. In addition to demonstrating the non-inferiority of levofloxacin compared with cefuroxime in AECOB, the data from this study raise the question of whether EFI is a useful discriminative endpoint for comparing antimicrobial therapies.

The efficacy and safety of oral pharmacokinetically enhanced amoxycillin-clavulanate 2000/125 mg, twice daily, versus oral amoxycillin-clavulanate 1000/125 mg, three times daily, for the treatment of bacterial community-acquired pneumonia in adults.

This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults. The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l. A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients). The most common pathogen isolated was S. pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group). In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4). The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively. The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85%. Both regimens were well tolerated, with no differences in adverse events between the groups. Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times daily, in patients with CAP and may also be appropriate for the treatment of infections due to S. pneumoniae strains with high-level penicillin resistance.